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DOI: 10.1055/s-0037-1607808
Activation of the Transcription factor Nrf2 involved in human trophoblast syncytialization (in vitro study)
Publikationsverlauf
Publikationsdatum:
27. Oktober 2017 (online)
Objectives:
Increased Oxidative stress and diminished oxidative capacity are distinctive features in the pregnancy-related syndrome preeclampsia and IUGR.
Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) initiates and enhances the transcription of many antioxidative enzymes, protecting the cells against oxidative injury.
Multinucleated syncytiotrophoblast (STB) layer acts as the first line of defence against placental oxidative stress. Cytotrophoblasts (CTB) differentiate and fuse with the STB to maintain the multi-nucleated layer.
It has been shown that Nrf2 is exclusively active within the CTB of preeclamptic placentas, a disturbed Trophoblast fusion has also been reported in preeclampsia. A link between Nrf2-signal-transduction pathways and trophoblast fusion has not yet been tested.
Methods:
We used the choriocarcinoma cell lines JEG 3 and BeWo to test the involvement of Nrf2 in the fusion process of the CTB. Using CellTrackerTM MoBiTec, the cells were stained in green and red, seeded together and stimulated with Nrf2-activator; Andographolide. Fusion process was observed via live cell imaging over 48 hours. Fused cells were recognized as orange-stained cells.
Results:
Activation of Nrf2 via Andrographolide enhanced the cell fusion when compared to the untreated cells. Furthermore, following the co-treatment with Andrographolide and Forskolin the cells showed an increase in the percentage of nuclei contained in syncytia compared to each substance alone.
Conclusion:
Our results suggest that the activation of Nrf2 via Andrographolide regulates the fusion of CTB-like cells. The induction of Nrf2 may be required for the development of the syncytiotrophoblast, as well as for normal placental and fetal development.
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